MYC/BCL2/BCL6 triple hit and TP53 deletion in a case of high-grade B cell lymphoma receiving CAR T cell immunotherapy

Abstract

High-grade B cell lymphoma with MYC, BCL2, and BCL6 rearrangements (HGBL-TH) is rare and often portends poor outcome after standard chemoimmunotherapy. Adoptive chimeric antigen receptor (CAR) T cell therapy is a new paradigm for the treatment of refractory/relapsed (r/r) lymphomas, but its therapeutic effects in treating HGBL-TH remain inconclusive. Here, we report a patient with HGBL-TH who failed to achieve complete remission (CR) and progressed rapidly after first-line and second-line therapies. Furthermore, he was resistant to the CAR19 and CAR22 T cell cocktail therapy following autologous hematopoietic stem cell transplantation (ASCT), and disease progressed again after the anti-B cell maturation antigen (BCMA) CAR T cell immunotherapy. Comprehensive analyses were performed to explore the inherent mechanism for resistance, which indicated that tumor-derived antigen escape, clonal evolution, and T cell defects were involved in it. This is the first report of an HGBL-TH patient with TP53 deletion and additional germline (PIM1) and somatic mutations (TP53, KMT2D, and IGLL5) who was treated with ASCT, CD19/22 CAR T cell cocktail therapy and BCMA CAR T cell immunotherapy. The clinical evolution and genetic features of this case may help to explain the underlying mechanism of treatment resistance and provide novel insights into lymphoma treatment. Trial registration: ChiCTR-OPN-16009847.